The purpose of this research is to define the mechanism(s) of renal protection afforded by splenectomy against acute renal failure (ARF). Acute renal failure can be produced in mongrel dogs by systemic infusion (i.v.) of epinephrine (Epi) (4 ug/kg/min) for 6 hours. Chronic splenectomy is found to afford significant protection against the development of this type of ARF. The mechanism(s) of renal protection in splenectomized dog remain unclear, however, the data suggest renal vasodilation and natriuresis (prostaglandins) as mediators of renal protection in chronic splenectomy model. Preliminary observations following treatment of intact and chronic splenectomy dogs with indomethacin (cyclo-oxygenase inhibitor) reveal consistent and progressive deterioration of renal function in chronic splenectomy dogs. Therefore, the available data allow us to propose that 1) prostaglandins (PGs) mediate renal protection in chronic splenectomy dog and 2) the spleen seems to inhibit PGs in some way causing ARF. These hypotheses will be tested by renal hemodynamic studies (renal blood flow, effective renal plasma flow, glomerular filtration rate, urinary sodium excretion and urinary osmolality) and renal histopathologic evaluations, and assays of urinary PGE2 and PGs biosynthesis in the kidney following treatment with indomethacin and following infusions of PGE2, PG12 (prostacyclin) alone or pretreated with indomethacin, and infusion with (C14) arachidonic acid in both intact and splenectomy dogs. Post-infusion follow-up of some dogs from each of the treated groups for a period of hours to no greater than six weeks with serial studies of serum urea nitrogen and creatinine concentrations and renal histopathology along with assays of urinary PGE2 and PGs biosynthesis in the kidney will allow the establishment of natural history of Epi-induced ARF and a mechanistic pathway defining renal protection in chronic splenectomy dog.